Per(poly)fluorinated polyoxyethylated carbamates

ABSTRACT

Per(poly)fluorinated polyoxyethylated carbamates of general formula (I) in which R F  represents a perfluorinated group containing between 1 and 18 carbon atoms, W represents an oxo group or nothing, n is an integer from 1 to 10, m is from values 2 to 6, 80 or not defined, R is an alkyl group, R F  W(CH 2 ) n+1  NHC(O)-- in which R F  and W are as defined above, --(CHCH 3  CH 2  O) 30  (CH 2  CH 2 ) 80  C(O)NH(CH 2 ) n+1  R F  in which R F  is a perfluorinated group containing from 1 to 18 carbon atoms, R&#39; is a hydrogen atom, an alkyl group containing between 1 and 18 carbon atoms which is optionally substituted, an optionally substituted aryl or aralkyl group, an allyl, methallyl or propargyl group or a perfluorinated chain having between 1 and 18 carbon atoms. These compounds can be used as anti-thrombosis agents or as surfactants or cosurfactants for phospholipids intended for the preparation or stabilization of fluorocarbon emulsions, notably emulsions for biomedical applications.

The invention relates to the synthesis of new per(poly)fluorinatedpolyoxyethylated carbamates. These compounds can be used as surfactantsor co-surfactants for phospholipids intended for the preparation orstabilisation of fluorocarbon emulsions, notably emulsions forbiomedical applications.

Non-ionic fluorinated surfactants are currently used in various fieldsof application, such as fire-fighting, the plastics, rubber andpetroleum industries, in the treatment of textiles, leather, paintings,pigments and coatings, mining and metallurgy, agriculture andsilviculture, photography and the graphic arts, in biomedicine todeactivate coated viruses and thus in the preparation of blood productswithout substantial denaturation of the plasma proteins etc.

Although in some cases it is possible to content oneself with mixturesof polyoxyethylated surfactants [J. Am. Chem. Soc. 106 (1984) 6162], thefiner applications (emulsions, microemulsions, gels etc.) occasionallydemand homogeneous compounds with perfectly defined structure and ofgreat purity, thus numerous monodisperse detergents have been developeddespite their high cost. In particular may be cited:

polyoxyethylated alcohols with the formula: R_(F) (CH₂)_(p) W(OH), wherep is generally less than 3, R_(F) is a perfluorinated chain, Wdesignates a chain of oxyethylene units (OC₂ H₄), where one or moreoxygen atoms may be replaced by sulphur atoms, are described inFR-A-2,565,226; R_(F) C₂ H₄ S(C₂ H₄ O)_(m) C₂ H₄ (C₂ H₄ O)_(n) Hpresenting oxyethylene and thioethyl groups which can be put together asdesired and the number of which can be controlled accurately [TensideSurf. Det. 31 51994) 124]; C_(n) F_(2n+1) CH₂ O(C₂ H₄ O)_(m) H which areexcellent emulsifiers of fluorocarbons [EP-A-0051526; Tetrahedron, 39,(1983) 1313; J. Am. Chem. Soc., 106 (1984 6162; Langmuir, 10 (1994)2131].

polyoxyethylated amides of the formulae: R_(F) CONHC₂ H₄ O)_(m) H [J.Fluorine Chem., 34 (1987) 385; R_(F) (CH₂)_(n) CONH(C₂ H₄ O)_(M) H [J.Chem. Research. (S), (1984) 292: J. Chem. Research (M), (1984) 2672],R_(F) C₂ H₄ NHCOC(CH₂ OH)₂ CH₃ [J. Chem. Soc., Chem. Commun., (1991)863], R_(F) C₂ H₄ CH(CONH(C₂ H₄ O)_(m) H)₂ (MC Patent No 2334 1996)],the product sold under the trade mark XMO-10 with the formula C₃ F₇O(CF₂)₃ CONH(CH₂)₃ N(O)(CH₃)₂ [Prog. Clin. Biol. Res., 122 (1983) 169];R_(F) (CH₂)_(p) C(O)N[OC₂ H₄)_(n) Me]₂ where p is generally less than 3.Products of this family where p=1 or 0 are described in French PatentApplication No 87.06515.

polyoxyethylated ethers with the formula R_(F) (CH₂)_(p) Q(C₂ H₄ O)_(n)Me where p is less than 5, in which R_(F) is a perfluorinated chain andQ designates groups such as --O(CH₂)₄ O--, --O(CH₂)₃ C(O)O--,--CH(OEt)CH₂ O-- [Biomat., Art. Cells, Biotech., 20 (1992) 115; J.Fluorine Chem., 68 (1994) 221].

polyfluorinated polyoxyethylated amines with the formula R_(F) C₂ H₄N[(C₂ H₄ O)_(m) R]₂ where m is 2 or 3, R_(F) is a perfluorinated chainand R represents a hydrogen atom or a methyl group [J. Colloid InterfaceSci., 177 (1996) 101].

perfluorinated glycosidic compounds used notably in the extraction andpurification of membrane proteins [New J. Chem., 1994, 18, 839] or inthe preparation of organised systems [Carbohydrates as Organic RawMaterials, Verlagsgesellschaft. (Ed), Weinheim, (1993) 209-259:Organofluorine Compounds in Medicinal Chemistry and BiomedicalApplications R Filler et al (Eds), Elsevier, (1993) 339-380].

This invention relates to the use of per(poly)fluorinatedpolyoxyethylated carbamates as anti-thrombosis agents or as a surfactantor as a co-surfactant for, in particular, phospholipids, especially ofegg yolk, to produce or stabilise emulsions, especially fluorocarbonemulsions intended, for example, for a biomedical application, forexample as injectable oxygen transporters (called "blood substitutes").The general formula for these carbamates is: ##STR1## in which R_(F)represents a perfluorinated group containing between 1 and 18 carbonatoms, W represents an oxo group or nothing, n is an integer from 1 to10, m is from 2 to 6, 80 or not defined, R is an alkyl group preferablycontaining between 1 and 4 carbon atoms, R_(F) W(CH₂)_(n+1) NHC(O)-- inwhich R_(F) and W have the same significance as above, or is --(CHCH₃CH₂ O)₃₀ (CH₂ CH₂ O)₈₀ C(O)NH(CH₂)_(n+1) R_(F) in which R_(F) is aperfluorinated group containing 1 to 18 or preferably 4 to 18 carbonatoms. R' is a hydrogen atom, an alkyl group containing between 1 and 18carbon atoms which is optionally substituted, an optionally substitutedaryl or optionally substituted aralkyl group, an allyl, methallyl orpropargyl group or a perfluorinated group with 1 to 18 or preferably 4to 18 carbon atoms. As substituents which may be present on the alkyl,aryl or aralkyl radicals, the hydroxyl or mercapto groups may be cited.As the perfluorinated groups may be mentioned perfluoroaliphatic groups,for example perfluoroalkyl; the perfluorinated groups may be branchedbut in one class of compounds are straight chain.

We have found that the invention enables the provision of componentswhich display a fairly good level of biological tolerance and do notcause haemolysis of red blood cells.

In one class of compounds. W is nothing. In another class, n is from 1to 4. A further class of compounds contain an R_(F) group which is alinear perfluorinated group containing 4, 6, 8 or 10 carbon atoms. Apreferred class of compounds contains all three of the aforesaidfeatures.

A yet further class of compounds are those compounds in which R' ishydrogen. In another class of compounds, R' is a said R' group otherthan hydrogen.

In one class of compounds W is oxo and R_(F) is optionally a linearperfluorinated group containing 1, 3, 4, 5, 6, 7, 8 or 10 carbon atoms.

Another class of compounds have an R group which is alkyl.

In general, the compounds of the invention are easily prepared bycondensation of oligoethylenes with per(poly)fluoroalkylated isocyanateswith satisfactory yields. So, for example, the compounds of theinvention in which W is nothing, n is between 1 and 10, m is from 2 to 6or not defined, R is an alkyl group preferably containing between 1 and4 carbon atoms, R' is a hydrogen atom and R_(F) a perfluorinatedaliphatic chain preferably comprising 4 to 18 carbon atoms, ie formula(II) compounds:

    R.sub.F (CH.sub.2).sub.n+1 NHC(O)O(CH.sub.2 CH.sub.2 O).sub.m R(II),

are formed quantitatively by the action of polyfluoroalkylatedisocyanates on the oligo- or poly-ethylenes. The reaction is bestconducted in an anhydrous atmosphere at a temperature of between 60 and70° C. for a period of 30 to 48 hours. The synthesis of the isocyanatesused as starting compounds has been described [MC Patent No 2349 (1996),J. Fluorine Chem. 56 (1992) 85].

As non-restrictive examples of partially protected oligoethylenes used,in particular there may be cited the following oligooxyethylenes:monomethyl ether of diethylene glycol, monoethyl ether of diethyleneglycol, monomethyl ether of triethylene glycol or monomethyl ethers ofpolyethylene glycol (which are commercial products) or monomethyl etherof tetraethylene glycol, monomethyl ether of pentaethylene glycol andmonomethyl ether of hexaethylene glycol, the preparation of which hasbeen described recently [Langmuir, 10 (1994) 2136]. However, the actionof the monomethyl ethers of polyethylene glycol on the isocyanates makesit possible to obtain polydisperse surfactant compounds.

Oligoethylenes such as tetraethylene glycol and pentaethylene glycolbehave in the same way towards the above-mentioned isocyanates andprovide formula (III) or formula (IV) dicarbamates.

    R.sub.F (CH.sub.2).sub.n+1 NHC(O)O(CH.sub.2 CH.sub.2 O).sub.m C(O)NH(CH.sub.2).sub.n+1 R.sub.F                          (III)

or

    R.sub.F C(O)(CH.sub.2).sub.n+1 NHC(O)O(CH.sub.2 CH.sub.2 O).sub.m C(O)NH(CH.sub.2).sub.n+1 C(O)R.sub.F                      (IV)

in which R_(F), n and m may be as defined in relation to Formula (I) andR_(F) preferably represents a perfluorinated group containing between 4and 18 carbon atoms, n is from 1 to 10 and m is preferably 4 or 5. Thesecompounds may be obtained by reacting two moles of isocyanate or, as thecase may be, oxoisocyanate with one mole of oligoethylene. In one classof Formula (III) compounds n is from 1 to 4; in another class R_(F) is alinear perfluorinated group containing 4, 6, 8 or 10 carbon atoms. SomeFormula (III) compounds belong to both classes. In one class of Formula(IV) compounds R_(F) is a linear perfluorinated group containing 1, 3,4, 5, 6, 7, 8 or 10 carbon atoms; in another class m is 3 or 4. SomeFormula (IV) compounds belong to both classes. A further class ofFormula (III) and (IV) compounds comprises compounds in which n is 3 or4 and/or m is 4 or 5.

The synthesis of the oxoisocyanates used as starting products forFormula (IV) compounds has been described already [MC Patent No 2350(1996) and the PCT application claiming priority therefrom, filed onJun. 24, 1997 under the title "Synthesis of GlycosidicPerfluoroaliphatic Surface-Active Agents by F2 Chemicals Ltd et al,which PCT application is included herein by reference].

By using Pluronic F-68 (commercial product, mp=54° C.) polydispersesurfactant compounds with the formula (V) are obtained. ##STR2## inwhich n is an integer from 1 to 10 and R_(F) is a perfluorinated grouppreferably containing between 4 and 18 carbon atoms. These compounds areprepared by the action of polyfluoroalkylated isocyanates on an excessof Pluronic F-68. In one class of Formula (V) compounds n is from 1 to4; in another class R_(F) is a linear perfluorinated group containing 4,6, 8 or 10 carbon atoms. Some Formula (V) compounds belong to bothclasses.

The use of isocyanates differently substituted with the partiallyprotected oligoethylenes gives rise to carbamates with the formula (VI).##STR3## in which R_(F) represents a perfluorinated group preferablycontaining between 4 and 18 carbon atoms, m takes the values 2 to 6 ornot defined, R is an alkyl group preferably containing between 1 and 4carbon atoms and R' represents an optionally substituted alkyl groupcontaining between 1 and 18 carbon atoms, an optionally substitutedaralkyl radical, an allyl, methallyl or propargyl radical or aperfluorinated chain preferably having 4 to 18 carbon atoms. As possiblesubstituents present on the alkyl, aryl or aralkyl radicals, thehydroxyl or mercapto groups may be cited.

The reaction may be performed in an anhydrous atmosphere at atemperature of, for example, between 60 and 70° C. for a period of 30 to48 hours. The branched isocyanates used as starting compounds aredescribed [MC Patent No 2349 (1996)].

Formula (I) compounds in which W is an oxo group, n is an integer of 1to 4 (preferably 3 or 4), m is preferably from 2 to 6 or a number whichis not defined, R' is a hydrogen atom, R is an alkyl group preferablycontaining between 1 and 4 carbon atoms and R_(F) represents aperfluorinated group containing between 1 and 18 carbon atoms (1, 3, 4,5, 6, 7, 8 or 10 carbon atoms in one class of compounds), ie formula(VII) compounds:

    R.sub.F C(O)(CH.sub.2).sub.n+1 NHC(O)O(CH.sub.2 CH.sub.2 O).sub.m R(VII)

are obtained by the condensation of partially protected oligoethyleneson the perfluoroalkylated oxoisocyanates.

The compounds of formulae (II)-(VII) and their sub-classes are eachdistinct classes of compounds of the invention.

The following Examples illustrate this invention without in any waylimiting it.

EXAMPLE 1.

Preparation of carbamates of the formula

    R.sub.F C.sub.2 H.sub.4 NHCO.sub.2 (C.sub.2 H.sub.4 O).sub.m CH.sub.3

where m=2 or 3.

An equimolar mixture of 2-F-alkylethyl isocyanate and monomethyl etherof diethylene glycol (or monomethyl ether of triethylene glycol) isheated to 65° C. for approximately 48 hours. It is then cooled toambient temperature. The carbamate formed is purified under a column ofsilica gel, eluant: ethyl acetate/petroleum ether: 5/5.

By way of example we give the yields and characteristics of somecompounds:

No.1. C₆ F₁₃ C₂ H₄ NHCO₂ (C₂ H₄ O)₂ CH₃ Yield=90% viscous liquid

Surface tension (0.1%, 25° C.)=19.3 mN/m.

I.R. (νcm⁻¹): 3332, 2878, 1719, 1300-1100 NMR of proton (CDCl₃ /TMS):2.40 (m, 2H, R_(F) CH₂); 3.4 (s, 3H, OCH₃); 3.7 (m, 8H, (C₂ H₄ O)₂);4.2(t, J=4.5 Hz, 2H, CH₂ N); 5.2 (t, J=5.4 Hz, 1H, NH) NMR of fluorine(CDCl₃ /CCl₃ F): -81 (3F,CF₃); -114.5 (2F, CF₂); -122 (2F,CF₂); -123(2F,CF₂); -124 (2F, CF₂); -127 (2F,CF₂).

No.2. C₆ F₁₃ C₂ H₄ NHCO₂ (C₂ H₄ O)₃ CH₃ Yield=90% liquid

Surface tension (0.1%, 25° C.)=15.9 mN/m.

I.R. (νcm⁻¹): 3332, 2878, 1719, 1300-1100 NMR of proton (CDCl₃ /TMS):2.40 (m, 2H, R_(F) CH₂); 3.4 (s, 3H, OCH₃); 3.7 (m, 12H, (C₂ H₄ O)₃);4.2 (t, J=4.5 Hz, 2H, CH₂ N); 5.2 (t, J=5.4 Hz, 1H, NH) NMR of fluorine(CDCl₃ /CCl₃ F): -81 (3F,CF₃); -115 (2F, CF₂); -122 (2F,CF₂); -123(2F,CF₂); -124 (2F, CF₂); -127 (2F,CF₂).

No.3. C₈ F₁₇ C₂ H₄ NHCO₂ (C₂ H₄ O)₂ CH₃ Yield=90% white solid

m.p.=40° C., b.p.=140° C./0.02 mm Hg,

Surface tension (0.1%, 25° C.)=18.6 mN/m.

I.R. (νcm⁻¹): 3322, 2878, 1697, 1300-1100 NMR of proton (CDCl₃ /TMS):2.40 (m, 2H, R_(F) CH₂); 3.4 (s, 3H, OCH₃); 3.7 (m, 8H, (C₂ H₄ O)₂); 4.2(t, J=4.5 Hz, 2H, CH₂ N); 5.2 (t, J=5.4 Hz, 1H, NH) NMR of fluorine(CDCl₃ /CCl₃ F): -81 (3F,CF₃); -114 (2F, CF₂); -122 (6F,CF₂); -123(2F,CF₂); -124 (2F,CF₂); -126 (2F, CF₂)

No.4. C₈ F₁₇ C₂ H₄ NHCO₂ (C₂ H₄ O)₃ CH₃ Yield=85% liquid

Surface tension (0.1%, 25° C.)=15.1 mN/n.

I.R. (νcm⁻¹): 3322, 2878, 1698, 1300-1100 NMR of proton (CDCl₃ /TMS):2.40 (m, 2H, R_(F) CH₂); 3.4 (s, 3H, OCH₃); 3.7 (m, 12H, (C₂ H₄ O)₃);4.2 (t, J=4.5 Hz, 2H, CH₂ N); 5.2 (t, J=5.4 Hz, 1H, NH) NMR of fluorine(CDCl₃ /CCl₃ F): -81 (3F,CF₃); -114 (2F, CF₂) -122 (6F,CF₂); -123(2F,CF₂); -124 (2F, CF₂); -126 (2F,CF₂)

EXAMPLE 2.

Preparation of carbamates with the formula

R_(F) C₃ H₆ NHCO₂ (C₂ H₄ O)_(m) CH₃ where m=2 or 3. The procedure is asabove (example 1), replacing 2-F-alkylethyl isocyanate with3-F-alkylpropyl isocyanate. The raw products formed are then purified ona silica column, eluant: diethyl ether oxide/petroleum ether (5/5).

By way of example we give the yields and characteristics of somecompounds:

No.1. C₄ F₉ C₃ H₆ NHCO₂ (C₂ H₄ O)₂ CH₃ Yield=90% liquid

Surface tension (0.1%, 25° C.)=19.3 mN/ m.

I.R. (νcm⁻¹): 3335, 2878, 1730, 1300-1100 NMR of proton (CDCl₃ /TMS):1.80 (m, 2H, C₄ F₉ CH₂ CH₂); 2.20 (m, 2H, R_(F) CH₂); 3.4 (s, 3H, OCH₃);3.7 (m, 8H, (C₂ H₄ O)₂); 4.2 (t, J=4.5 Hz, 2H, CH₂ N); 5.1 (t, J=5.4 Hz,1H, NH) NMR of fluorine (CDCl₃ /CCl₃ F): -81 (3F,CF₃); -115 (2F, CF₂);-124 (2F,CF₂); -126 (2F,CF₂)

No.2. C₆ F₁₃ C₃ H₆ NHCO₂ (C₂ H₄ O)₂ CH₃ Yield=87% liquid

Surface tension (0.1%, 25° C.)=19.4 mN/m.

I.R. (νcm⁻¹): 3344, 2878, 1729, 1300-1100 NMR of proton (CDCl₃ /TMS):1.80 (m, 2H, C₆ F₁₃ CH₂ CH₂); 2.20 (m, 2H, R_(F) CH₂); 3.4 (s, 3H,OCH₃); 3.7 (m, 8H, (C₂ H₄ O)₂); 4.2 (t, J=4.5 Hz, 2H, CH₂ N); 5.1 (t,J=5.4 Hz, 1H, NH) NMR of fluorine (CDCl₃ /CCl₃ F): -81 (3F,CF₃); -115(2F, CF₂); -122 (2F,CF₂); -123 (2F,CF₂); -124 (2F, CF₂); -127 (2F,CF₂).

No.3. C₆ F₁₃ C₃ H₆ NHCO₂ (C₂ H₄ O)₃ CH₃ Yield=90% liquid

Surface tension (0.1%, 25° C.) =16.1 mN/m.

I.R. (νcm⁻¹): 3334, 2878, 1721, 1300-1100 NMR of proton (CDCl₃ /TMS):1.80 (m, 2H, C₆ F₁₃ CH₂ CH₂); 2.20 (m, 2H, R_(F) CH₂); 3.4 (s, 3H,OCH₃); 3.6 (m, 12H, (C₂ H₄ O)₃); 4.2 (t, J=4.5 Hz, 2H, CH₂ N); 5.1 (t,J=5.4 Hz, 1H, NH) NMR of fluorine (CDCl₃ /CCl₃ F): -81 (3F,CF₃); -115(2F, CF₂); -122 (2F,CF₂); -123 (2F,CF₂);-124 (2F, CF₂); -127 (2F,CF₂)

No.4. C₈ F₁₇ C₃ H₆ NHCO₂ (C₂ H₄ O)₂ CH₃ Yield=90% liquid

Surface tension (0.1%, 25° C.)=15.8 mN/m.

I.R. (νcm⁻¹): 3334, 2878, 1715, 1300-1100 NMR of proton (CDCl₃ /TMS):1.80 (m, 2H, C₈ F₁₇ CH₂ CH₂); 2.20 (m, 2H, R_(F) CH₂); 3.4 (s, 3H,OCH₃); 3.7 (m, 8H, (C₂ H₄ O)₂); 4.2 (t, J=4.5 Hz, 2H, CH₂ N); 5.1 (t,J=5.4 Hz, 1H, NH) NMR of fluorine (CDCl₃ /CCl₃ F): -81 (3F,CF₃); -114(2F, CF₂); -122 (6F, 3 CF₂); -123 (2F,CF₂); -124 (2F, CF₂); -127(2F,CF₂).

No.5. C₈ F₁₇ C₃ H₆ NHCO₂ (C₂ H₄ O)₃ CH₃ Yield=90% pasty product

Surface tension (0.1%, 25° C.) =15.3 mN/m.

I.R. (νcm⁻¹): 3335, 2878, 1730, 1300-1100 NMR of proton (CDCl₃ /TMS):1.80 (m, 2H, C₈ F₁₇ CH₂ CH₂); 2.20 (m, 2H, R_(F) CH₂); 3.4 (s, 3H,OCH₃); 3.7 (m, 12H, (C₂ H₄ O)₃); 4.2 (t, J=4.5 Hz, 2H, CH₂ N); 5.1 (t,J=5.4 Hz, 1H, NH) NMR of fluorine (CDCl₃ /CCl₃ F): -81 (3F,CF₃); -114.5(2F, CF₂); -122 (6F, 3 CF₂); -123 (2F,CF₂); -124 (2F,CF₂); -127(2F,CF₂).

EXAMPLE 3.

Preparation of carbamates with the formula:

    R.sub.F C.sub.2 H.sub.4 NHCO.sub.2 (C.sub.2 H.sub.4 O).sub.m C(O)NHC.sub.2 H.sub.4 R.sub.F

where m=4 or 5.

The procedure is as above (example 1). The raw products formed by thecondensation of 0.002 of a mole of 2-F-alkylethyl isocyanate with 0.001of a mole of oligoethylene are then purified by recrystallization inchloroform.

By way of example we give the yields and characteristics of somecompounds:

No.1. C₈ F₁₇ C₂ H₄ NHCO₂ (C₂ H₄ O)₄ C(O)NHC₂ H₄ C₈ F₁₇ Yield=85% whitesolid

m.p.=75°, very slightly soluble in water.

NMR of proton (acetone d₆ /TMS): 2.50 (m, 4H, 2×R_(F) CH₂); 3.6 (m, 16H,(C₂ H₄ O)₄); 4.2 (t, J=4.6 Hz, 4H, CH₂ N); 6.6 (t, J=5.4 Hz, 2H, NH) NMRof fluorine (acetone d₆ /CCl₃ F): -81 (CF₃); -114 (CF₂): -122 (3 CF₂);-123 (CF₂); -124 (CF₂); -127 (CF₂).

No.2. C₈ F₁₇ C₂ H₄ NHCO₂ (C₂ H₄ O)₅ C(O)NHC₂ H₄ C₈ H₁₇ Yield 85% whitesolid

m.p.=67° C. very slightly soluble in water.

NMR of proton (acetone d₆ /TMS): 2.50 (m, 4H, R_(F) CH₂); 3.6 (m, 20H,(C₂ H₄ O)₅); 4.2 (t, J=4.6 Hz, 4H, CH₂ N); 6.5 (t, J=5.4 Hz, 2H, 2×NH)

NMR of fluorine (acetone d₆ /CCl₃ F): -81 (CF₃); -114 (CF₂); -122 (3CF₂); -123 (CF₂); -124 (CF₂); -127 (CF₂).

EXAMPLE 4.

Preparation of carbamates with the formula:

    R.sub.F C.sub.2 H.sub.4 CH(R')NHCO.sub.2 (C.sub.2 H.sub.4 O).sub.3 CH.sub.3

where m=2 or 3.

The procedure is as above (example 1), replacing 2-F-alkylethylisocyanate with a ramified isocyanate. The raw products formed are thenpurified on a silica column.

eluant: ethyl acetate/Methanol 9:1.

By way of example we give the yields and characteristics of somecompounds:

No.1. C₄ F₉ C₂ H₄ CH[CH₃ (CH₂)₁₀ ]NHCO₂ (C₂ H₄ O)₃ CH₃ Yield=90% liquid

Surface tension (0.1%, 25° C.)=29.1 mN/m.

I.R. (νcm⁻¹): 3321, 2926, 2854, 1696, 1300-1100 NMR of proton (CDCl₃/TMS): 0.9 (t, J=6.48 Hz, 3H, CH₂); 1.30 (m, 18H, CH₃ (CH₂)₉); 1.6-2.2(m, 6H, R_(F) CH₂ CH₂, CH₃ (CH₂)₉ CH₂), 3.4 (s, 3H, OCH₃); 3.7 (m, 12H,(C₂ H₄ O)₃); 4.2 (m, 1H, CHNHCO₂); 4.7 (m, 1H, NCHO₂); NMR of fluorine(CDCl₃ /CCl₃ F): -81 (3F,CF₃); -115 (2F, CF₂); -124(2F,CF₂); -126(2F,CF₂).

No.2. C₆ F₁₃ C₂ H₄ CH[CH₃ (CH₂)₈ ]NHCO₂ (C₂ H₄ O)₂ CH₃ Yield=90% liquid

Surface tension (0.1%, 25° C.)=30.0 mN/m.

I.R. (νcm⁻¹): 3320, 2926, 2854, 1697, 1300-1100 NMR of proton (CDCl₃/TMS): 0.9 (t, J=6.53 Hz, 3H, CH₃); 1.30 (m, 14H, CH₃ (CH₂)₇); 1.6-2.2(m, 6H, R_(F) CH₂ CH₂, CH₃ (CH₂)₇ CH₂), 3.4 (s, 3H, OCH₃); 3.7 (m, 8H,(C₂ H₄ O)₂); 4.2 (m, 1H, CHNHCO₂); 4.7 (m, 1H, NCHO₂); NMR of fluorine(CDCl₃ /CCl₃ F): -81 (3F,CF₃); -115 (2F, CF₂); -122 (2F,CF₂); -123(2F,CF₂); -124(2F,CF₂); -127 (2F,CF₂).

No.3. C₆ F₁₃ C₂ H₄ CH[CH₃ (CH₂)₈ ]NHCO₂ (C₂ H₄ O)₃ CH₃ Yield=90% liquid

Surface tension (0.1%, 25° C.)=25.6 mN/m.

I.R. (νcm⁻¹): 3318, 2927, 2856, 1694, 1300-1100 NMR of proton (CDCl₃/TMS): 0.9 (t, J=6.58 Hz, 3H, CH₃); 1.30 (m, 14H, CH₃ (CH₂)₇); 1.6-2.2(m, 6H, R_(F) CH₂ CH₂, CH₃ (CH₂)₇ CH₂), 3.4 (s, 3H, OCH₃); 3.7 (m, 12H,(C₂ H₄ O)₃); 4.2 (m, 1H, CHNHCO₂); 4.7 (m, 1H, NHCO₂); NMR of fluorine(CDCl₃ /CCl₃ F): -81 (3F,CF₃); -115 (2F,CF₂); -122 (2F,CF₂); -123(2F,CF₂); -124 (2F, CF₂); -127 (2F,CF₂).

No.4. C₆ F₁₃ C₂ H₄ CH[CH₃ (CH₂)₉ ]NHCO₂ (C₂ H₄ O)₂ CH₃ Yield=90% liquid

Surface tension (0.1%, 25° C.)=29.0 mN/m.

I.R. (νcm⁻¹): 3318, 2927, 2856, 1694, 1300-1100 NMR of proton (CDCl₃/TMS): 0.9 (t, J=6.58 Hz, 3H, CH₃); 1.30 (m, 16H, CH₃ (CH₂)₈); 1.6-2.2(m, 6H, R_(F) CH₂ CH₂, CH₃ (CH₂)₈ CH₂), 3.4 (s, 3H, OCH₃); 3.7 (m, 8H,(C₂ H₄ O)₂); 4.2 (m, 1H, CHNHCO₂ ; 4.7 (m, 1H, NHCO₂); NMR of fluorine(CDCl₃ /CCl₃ F): -81 (3F,CF₃); -115 (2F,CF₂); -122 (2F,CF₂); -123(2F,CF₂); -124 (2F,CF₂); -127 (2F,CF₂).

No.5. C₆ F₁₃ C₂ H₄ CH[CH₃ (CH₂)₉ ]NHCO₂ (C₂ H₄ O)₃ CH₃ Yield=90% liquid

Surface tension (0.1%, 25° C.) 23.2 mN/m.

I.R. (νcm⁻¹) 3318, 2927, 2856, 1694, 1300-1100 NMR of proton (CDCl₃/TMS): 0.9 (t, J=6.58 Hz, 3H, CH₃); 1.30 (m, 16H, CH₃ (CH₂)₈); 1.6-2.2(m, 6H, R_(F) CH₂ CH₂, CH₃ (CH₂)₈ CH₂); 3.4 (s, 3H, OCH₃); 3.7 (m, 12H,(C₂ H₄ O)₃); 4.2 (m, 1H, CHNHCO₂); 4.7 (m, 1H, NHCO₂); NMR of fluorine(CDCl₃ /CCl₃ F): -81 (3F,CF₃); -115 (2F, CF₂); -122 (2F,CF₂); -123(2F,CF₂); -124 (2F,CF₂); -127 (2F,CF₂).

No.6. C₆ F₁₃ C₂ H₄ CH[CH₃ (CH₂)₁₅ ]NHCO₂ (C₂ H₄ O)₃ CH₃ Yield=80% whitesolid

m.p.=38° C., insoluble in water.

NMR of proton (CDCl₃ /TMS): 0.9 (t, J=6.52 Hz, 3H, CH₃); 1.30 (m, 28H,CH₃ (CH₂)₁₄); 1.6-2.2 (m, 6H, R_(F) CH₂ CH₂, CH₃ (CH₂)₁₄ CH₂); 3.4 (s,3H, OCH₃); 3.7 (m, 12H, (C₂ H₄ O)₃); 4.2 (m, 1H, CHNHCO₂); 4.7 (m, 1H,NHCO₂); NMR of fluorine (CDCl₃ /CCl₃ F): -81 (3F,CF₃); -115 (2F,CF₂);-122 (2F,CF₂); -123 (2F,CF₂); -124 (2F,CF₂); -127 (2F,CF₂).

No.7. C₈ F₁₇ C₂ H₄ CH[CH₃ (CH₂)₁₁ ]NHCO₂ (C₂ H₄ O)₃ CH₃ Yield=90% pastysolid

Surface tension (0.1%, 25° C.)=20.3 mN/m.

I.R. (νcm⁻¹) 3320, 2925, 2855, 1694, 1300-1100 NMR of proton (CDCl₃/TMS): 0.9 (t, J=6.58 Hz, 3H, CH₃); 1.30 (m, 20H, CH₃ (CH₂)₁₀); 1.6-2.2(m, 6H, R_(F) CH₂ CH₂, CH₃ (CH₂)₁₀ CH₂); 3.4 (s, 3H, OCH₃); 3.7 (m, 12H,(C₂ H₄ O)₃); 4.2 (m, 1H, CHNHCO₂); 4.7 (m, 1H, NHCO₂); NMR of fluorine(CDCl₃ /CCl₃ F): -81 (3F,CF₃); -114 (2F,CF₂); -122 (6F,CF₂); -123(2F,CF₂); -124 (2F,CF₂); -127 (2F,CF₂)

EXAMPLE 5.

Preparation of the carbamate with the formula:

    C.sub.7 F.sub.15 C(O)CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 NHCO.sub.2 (C.sub.2 H.sub.4 O).sub.2 CH.sub.3

The procedure is as above (example 1), replacing 2-F-alkylethylisocyanate with a perfluoroalkylated oxoisocyanate. The raw productformed in this way is then purified by recrystallization in hexane.

C₇ F₁₅ C(O)CH₂ CH₂ CH₂ CH₂ NHCO₂ (C₂ H₄ O)₂ CH₃ Yield=85% white solid

m.p.=43°, surface tension (0.1%, 25° C.)=16.1 mN/m.

NMR of proton (CDCl₃ /TMS): 1.60 (m, 4H, C₂ H₄); 2.80 (t, 2H, J=5.4 HzCH₂ C(O)); 3.4 (s, 3H, OCH₃); 3.7 (m, 8H, (C₂ H₄ O)₂); 4.2 (t, J=4.5 Hz,2H, CH₂ N); 4.8 (t, J=5.4 Hz, 1H, NH) NMR of fluorine (CDCl₃ /CCl₃ F):-81 (3F,CF₃); -120 (2F,CF₂); -121 (2F,CF₂); -122.5 (4F,2CF₂); -122.8(2F,CF₂); -127 (2F,CF₂).

Further aspects of the invention as well as preferred embodimentsthereof are set forth in the following claims.

What is claimed is:
 1. A per(poly)fluorinated polyoxyethylated carbamateof the general formula: ##STR4## in which R_(F) represents aperfluorinated group containing between 1 and 18 carbon atoms, Wrepresents an oxo group or nothing, n is an integer from 1 to 10, m isfrom values 2 to 6 or 80, R is an alkyl group, R_(F) W(CH₂)_(n+1)NHC(O)-- in which R_(F) and W are as defined above, --(CHCH₃ CH₂ O)₃₀(CH₂ CH₂ O)₈₀ C(O)NH(CH₂)_(n+1) R_(F) in which R_(F) is a perfluorinatedgroup containing from 1 to 18 carbon atoms, R' is a hydrogen atom, analkyl group containing between 1 and 18 carbon atoms which is optionallysubstituted, an optionally substituted aryl or aralkyl group, an allyl,methallyl or propargyl group or a perfluorinated chain having between 1and 18 carbon atoms.
 2. A compound of claim 1, in which W is nothing. 3.A compound of claim 1, in which R' is a hydrogen atom.
 4. A compound ofclaim 1, in which R' is an alkyl group containing between 1 and 18carbon atoms which is optionally substituted, an optionally substitutedaryl or aralkyl group, an allyl, methallyl or propargyl radical orperfluorinated chain having from 4 to 18 carbon atoms.
 5. A compound ofclaim 1, in which the optional substituent(s) on the alkyl, aryl oraralkyl groups is/are selected from hydroxyl and mercapto.
 6. A compoundof claim 1, in which n is from 1 to 4 and/or m is from 2 to
 6. 7. Acompound of claim 1, in which R contains from 1 to 4 carbon atoms.
 8. Acompound of claim 1, in which R_(F) is a linear perfluorinated groupcontaining 4, 6, 8 or 10 carbon atoms.
 9. A compound of claim 1, inwhich R_(f) is a linear perfluorinated group containing 4, 6, 8, or 10carbon atoms, n is from 1 to 4, and W is nothing.
 10. A compound ofclaim 1, in which W is an oxo group.
 11. A compound of claim 10, inwhich R_(F) is a linear perfluorinated group containing 1, 3, 4, 5, 6,7, 8 or 10 carbon atoms.